crossing96/oncoscreening huggingface dataset:
Non-Small Cell Lung Cancer as a Second Primary Among Patients With Previous Malignancy: Who Is at Risk?	BACKGROUND: Patients with previous malignancies could be at increased risk of non-small cell lung cancer (NSCLC). However, the extent of the risk is unknown for many cancer types; thus, it is unclear who might benefit from screening. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results data set from 1992 to 2012 was used to identify patients with previous malignancies who received a diagnosis of NSCLC ≥ 6 months after their initial cancer diagnosis. Standardized incidence ratios (SIRs) for NSCLC were calculated as a ratio of the observed to expected cases adjusted by person-years at risk. Cancers with a SIR > 1.0 had a risk of NSCLC greater than expected. The analyses were stratified by sex, radiation therapy use, and histologic type. RESULTS: Among the cancer survivors, 32,058 developed NSCLC. Smoking-related (lung, head and neck, bladder) and hematologic malignancies, regardless of previous radiation therapy, had the greatest SIR for NSCLC (range, 1.97-4.88). Colorectal and renal cancer survivors also had an increased SIR for NSCLC (1.16 and 1.21, respectively). Women with previous pancreatic cancer treated with radiation, breast cancer with or without radiation therapy, and those with thyroid cancer demonstrated a greater SIR for lung adenocarcinoma. Men with previous irradiated prostate cancer also had an elevated SIR (1.08; 99% confidence interval, 1.01-1.15) for lung adenocarcinoma. Patients with melanoma, prostate or uterine cancer had a lower SIR for NSCLC than expected. CONCLUSION: Smoking-related malignancies had the greatest risk of NSCLC. Radiation therapy conferred an elevated risk of NSCLC for certain cancers. Melanoma, prostate, and uterine cancer survivors had a low risk of NSCLC. These results could help identify high-risk screening candidates in the growing population of cancer survivors.	bladder
W-pouch With Modified Non-isolated Extra Limb for Continence in Cutaneous Diversion After Radical Cystectomy.	OBJECTIVE: To report the functional results of continent cutaneous ileal urinary diversion using modified W-pouch with non-isolated extra limb for continence. PATIENTS AND METHODS: From January 2013 to January 2016, 21 patients with muscle-invasive bladder cancer with median (interquartile range) of 59 (56.5-62.5) years old underwent radical cystectomy with pelvic lymphadenectomy; they then had an ileal continent cutaneous pouch constructed from W-pouch with non-isolated extra limb for continence. The technique entails the creation of a detubularized ileal W-pouch with extra limb fashioned from 59 cm of the terminal ileum. This extra limb is not isolated from the pouch. The proximal part of this limb is tailored and fixed in a subserous extramural tunnel for continence, whereas the distal part is left continuous with the pouch. The median (interquartile range) of follow up was 12 (8-17) months. Evaluation of the technique included operative time, continence efficiency, overall complications, and quality of life questionnaire for the patients. RESULTS: The median (interquartile range) of operative time of the operation was 4.7 (3.9-5.4) hours. The median (interquartile range) of operative time of the cutaneous pouch creation was 39 (33-43) minutes. No perioperative mortality had occurred. The incidence of continence was 95.2%. The overall complications were 42.8%, and most of them were grade 1 or 2 on Clavien-Dindo classification system. CONCLUSION: Modification of W-pouch with non-isolated extra limb as continent cutaneous pouch can simplify the technique and shorten the operative time with efficient continence, less side effects, and good quality of life.	bladder
An Oncofetal Glycosaminoglycan Modification Provides Therapeutic Access to Cisplatin-resistant Bladder Cancer.	BACKGROUND: Although cisplatin-based neoadjuvant chemotherapy (NAC) improves survival of unselected patients with muscle-invasive bladder cancer (MIBC), only a minority responds to therapy and chemoresistance remains a major challenge in this disease setting. OBJECTIVE: To investigate the clinical significance of oncofetal chondroitin sulfate (ofCS) glycosaminoglycan chains in cisplatin-resistant MIBC and to evaluate these as targets for second-line therapy. DESIGN, SETTING, AND PARTICIPANTS: An ofCS-binding recombinant VAR2CSA protein derived from the malaria parasite Plasmodium falciparum (rVAR2) was used as an in situ, in vitro, and in vivo ofCS-targeting reagent in cisplatin-resistant MIBC. The ofCS expression landscape was analyzed in two independent cohorts of matched pre- and post-NAC-treated MIBC patients. INTERVENTION: An rVAR2 protein armed with cytotoxic hemiasterlin compounds (rVAR2 drug conjugate [VDC] 886) was evaluated as a novel therapeutic strategy in a xenograft model of cisplatin-resistant MIBC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Antineoplastic effects of targeting ofCS. RESULTS AND LIMITATIONS: In situ, ofCS was significantly overexpressed in residual tumors after NAC in two independent patient cohorts (p<0.02). Global gene-expression profiling and biochemical analysis of primary tumors and cell lines revealed syndican-1 and chondroitin sulfate proteoglycan 4 as ofCS-modified proteoglycans in MIBC. In vitro, ofCS was expressed on all MIBC cell lines tested, and VDC886 eliminated these cells in the low-nanomolar IC(50) concentration range. In vivo, VDC886 effectively retarded growth of chemoresistant orthotopic bladder cancer xenografts and prolonged survival (p=0.005). The use of cisplatin only for the generation of chemoresistant xenografts are limitations of our animal model design. CONCLUSIONS: Targeting ofCS provides a promising second-line treatment strategy in cisplatin-resistant MIBC. PATIENT SUMMARY: Cisplatin-resistant bladder cancer overexpresses particular sugar chains compared with chemotherapy-naïve bladder cancer. Using a recombinant protein from the malaria parasite Plasmodium falciparum, we can target these sugar chains, and our results showed a significant antitumor effect in cisplatin-resistant bladder cancer. This novel treatment paradigm provides therapeutic access to bladder cancers not responding to cisplatin.	bladder
Topical and systemic immunoreaction triggered by intravesical chemotherapy in an N-butyl-N-(4-hydroxybutyl) nitorosamine induced bladder cancer mouse model.	Intravesical bacillus Calmette-Guerin (BCG) treatment is the most common therapy to prevent progression and recurrence of non-muscle invasive bladder cancer (NMIBC). Although the immunoreaction elicited by BCG treatment is well documented, those induced by intravesical treatment with chemotherapeutic agents are much less known. We investigated the immunological profiles caused by mitomycin C, gemcitabine, adriamycin and docetaxel in the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced orthotopic bladder cancer mouse model. Ninety mice bearing orthotopic bladder cancer induced by BBN were randomly divided into six groups and treated with chemotherapeutic agents once a week for four weeks. After last treatment, bladder and serum samples were analyzed for cell surface and immunological markers (CD4, CD8, CD56, CD204, Foxp3, and PD-L1) using immunohistochemistry staining. Serum and urine cytokine levels were evaluated by ELISA. All chemotherapeutic agents presented anti-tumor properties similar to those of BCG. These included changes in immune cells that resulted in fewer M2 macrophages and regulatory T cells around tumors. This result was compatible with those in human samples. Intravesical chemotherapy also induced systemic changes in cytokines, especially urinary interleukin (IL)-17A and granulocyte colony stimulating factor (G-CSF), as well as in the distribution of blood neutrophils, lymphocytes, and monocytes. Our findings suggest that intravesical treatment with mitomycin C and adriamycin suppresses protumoral immunity while enhancing anti-tumor immunity, possibly through the action of specific cytokines. A better understanding of the immunoreaction induced by chemotherapeutic agents can lead to improved outcomes and fewer side effects in intravesical chemotherapy against NMIBC.	bladder
Occupational exposures and genetic susceptibility to urinary tract cancers: a systematic review and meta-analysis.	This study aims to summarize the current knowledge on the relationship between genetic polymorphisms, occupational exposures, and urinary tract cancers. We searched MEDLINE, ISI Web of science, and SCOPUS online databases for all articles published in English language up to September 2016. A meta-analysis was performed to provide summary estimates for the association between a certain genetic polymorphism, occupational exposure and bladder cancer (BC) or kidney cancer (KC), when appropriate. Fifteen studies on BC and six on KC were deemed eligible for the review. With regard to BC, an overall odds ratio (OR) of 2.07 [95% confidence interval (CI): 1.38-3.09] for those with GSTM1 and an OR of 2.07 (95% CI: 1.38-3.09) for those with GSTT1 null genotype were reported when exposed to polycyclic aromatic hydrocarbons (PAHs). NAT2 slow genotype carriers had an OR of 3.59 (95% CI: 2.62-4.93) for BC when exposed to aromatic amines and an OR of 2.07 (95% CI: 1.36-3.15) when exposed to PAHs. With regard to KC and pesticide exposure, the meta-analysis reported an OR of 4.38 (95% CI: 2.28-8.41) for GSTM1 present genotype, an OR of 2.59 (95% CI: 1.62-4.15) for GSTT1-present genotype and an OR of 6.51 (95% CI: 2.85-14.89) for combined effects of GSTM1 and GSTT1 active genotypes. This meta-analysis indicates a possible association between the variant genotypes of GSTM1, GSTT1, NAT2 and SULT1A1, occupational exposure to aromatic amines or PAHs, and development of BC. Our results suggest that polymorphisms in GSTM1 and GSTT1 genes could influence the risk for developing KC in individuals occupationally exposed to pesticides.	bladder
"The value of the UroVysion® FISH assay in the risk-stratification of patients with ""atypical urothelial cells"" in urinary cytology specimens."	"BACKGROUND: The aim of this study was to evaluate the potential use of the UroVysion® fluorescent in situ hybridization test (U-FISH) to stratify the risk of urothelial carcinoma (UC) in patients with a diagnosis of ""atypical urothelial cells"" (AUC) in urinary tract cytology (UTCy). METHODS: Using a histologic diagnosis of UC and respectively of high grade UC (HGUC) within 12 months of the index UTCy as a reference standard, we determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of U-FISH for patients with AUC diagnosed 2008 to 2014. RESULTS: Of the 377 patients with AUC, 62 (16.45%) were diagnosed with UC (29 low grade UC and 33 HGUC) within 12 months. U-FISH were uninformative in 45 (11.94%), positive in 63 (16.71%) and negative in 269 (71.35%). UC was diagnosed more frequently in patients with positive than in those with negative U- FISH results (31/63, 49.21% vs. 25/269, 9.29%, P < 0.0001). The sensitivity, specificity, PPV, NPV and accuracy of U-FISH in the setting of AUC were 44.64%, 81.82%, 47.17%, 80.25%, and 71.91% for UC and respectively 48.39%, 78.77%. 28.3%, 89.81%, and 74.29% for HGUC. U-FISH showed a high false positive rate (28/53, 52.83%) that remained high even after extended follow-up, arguing against ""anticipatory positive"" results. CONCLUSIONS: U-FISH allows risk stratification in patients with AUC. However, its usefulness is diminished by the high false-positive rate, making it important to interpret U- FISH results in the patient's clinical context. Diagn. Cytopathol. 2017;45:481-500. © 2017 Wiley Periodicals, Inc."	bladder
[Vesical urothelial papilloma].	INTRODUCTION: Vesical tumors of infancy are of a low incidence and isolated clinical cases exist, and therefore there are no protocols regarding treatment and monitoring. In addition, the histological criteria used until now are the ones in the WHO 2004 guidelines. CLINICAL CASE: A 11 year old boy with non-specific abdominal pain. Upon abdominal ultrasound a tumor is observed near the left ureteral orifice, and proceeding with Thulium laser vaporization, a histological diagnosis is made: vesical urothelial papilloma. COMMENTS: Different diagnostic and therapeutic methods are discussed, with particular emphasis on the importance of a correct diagnosis due to risk of confusion with carcinomas. Despite benign, there is a risk of malignant progression and we recommend pursuing clinical follow-ups and periodical ultrasounds, performing cystoscopy in case of suspicious findings on ultrasound.	bladder
The prognostic significance of DAPK1 in bladder cancer.	Bladder cancer is one of the leading causes of cancer-related death in men, however, there was only limited effective treatment for invasive bladder cancer. DAPK1 has been shown to play important role in apoptosis and autophagy to suppress cancer progression. Previous results have shown that DAPK1 promoter was hypermethylated in the majority of bladder cancer specimens, however, the prognostic significance of DAPK1 in bladder cancer has yet to be demonstrated. In the present study, we found that DAPK1 expression was negatively associated with tumor stage and a low level expression of DAPK1 in bladder cancer specimens were associated with shorter survival in bladder cancer patients in 3 independent bladder cancer datasets (n = 462). Further investigation showed that FGFR3 knockdown resulted in downregulation of DAPK1 in bladder cancer cell line, suggesting that FGFR3 may be an upstream factor of DAPK1. Further analysis of the 3 independent bladder cancer datasets have identified ACOX1, UPK2, TRAK1, PLEKHG6 and MT1X genes had their expression significantly correlated with that of DAPK1. Knockdown of DAPK1 in bladder cancer T24 cells resulted in downregulation of ACOX1, UPK2 and TRAK1. Interestingly, TRAK1, by itself, was a favorable prognostic marker in the 3 independent bladder cancer datasets. Importantly, by using connectivity mapping with DAPK1-associated gene signature, we found that vemurafenib and trametinib could possibly reverse DAPK1-associated gene signature, suggesting that inhibition of Raf/MEK pathway may be a potential therapeutic approach for bladder cancer. Indeed, treatment of vemurafenib in T24 bladder cancer cells resulted in upregulation of DAPK1 confirming our connectivity mapping, while knockdown of DAPK1 resulted in reduced sensitivity towards inhibition of Braf signaling by vemurafenib. Together, our results suggest that DAPK1 is an important prognostic marker and therapeutic target for bladder cancer and have identified possible therapeutic agents for future testing in bladder cancer models with low DAPK1 expression.	bladder
Inhibition of Pyruvate Kinase M2 Markedly Reduces Chemoresistance of Advanced Bladder Cancer to Cisplatin.	Chemoresistance to cisplatin is a principal cause of treatment failure and mortality of advanced bladder cancer (BC). The underlying mechanisms remain unclear, which hinders the development of preventive strategies. Recent data indicate that pyruvate kinase M2 (PKM2), a glycolytic enzyme for Warburg effect, is strongly upregulated in BC. This study explores the role of PKM2 in chemoresistance and whether inhibiting PKM2 augments the chemosensitivity to cisplatin and reduces BC growth and progression. We found that Shikonin binds PKM2 and inhibits BC cell survival in a dose-dependent but pyruvate kinase activity-independent manner. Down-regulation of PKM2 by shRNA blunts cellular responses to shikonin but enhances the responses to cisplatin. Shikonin and cisplatin together exhibit significantly greater inhibition of proliferation and apoptosis than when used alone. Induced cisplatin-resistance is strongly associated with PKM2 overexpression, and cisplatin-resistant cells respond sensitively to shikonin. In syngeneic mice, shikonin and cisplatin together, but not as single-agents, markedly reduces BC growth and metastasis. Based on these data, we conclude that PKM2 overexpression is a key mechanism of chemoresistance of advanced BC to cisplatin. Inhibition of PKM2 via RNAi or chemical inhibitors may be a highly effective approach to overcome chemoresistance and improve the outcome of advanced BC.	bladder
Down-regulation of LncRNA TUG1 enhances radiosensitivity in bladder cancer via suppressing HMGB1 expression.	BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to regulate the sensitivity of different cancer cells to chemoradiotherapy. Aberrant expression of lncRNA Taurine-upregulated gene 1 (TUG1) has been found to be involved in the development of bladder cancer, however, its function and underlying mechanism in the radioresistance of bladder cancer remains unclear. METHODS: Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of TUG1 and HMGB1 mRNA in bladder cancer tissues and cell lines. HMGB1 protein levels were tested by western blot assays. Different doses of X-ray were used for radiation treatment of bladder cancer cells. Colony survival and cell viability were detected by clonogenic assay and CCK-8 Kit, respectively. Cell apoptosis was determined by flow cytometry. A xenograft mouse model was constructed to observe the effect of TUG1 on tumor growth in vivo. RESULTS: The levels of TUG1 and HMGB1 were remarkably increased in bladder cancer tissues and cell lines. Radiation treatment markedly elevated the expression of TUG1 and HMGB1. TUG1 knockdown inhibited cell proliferation, promoted cell apoptosis and decreased colony survival in SW780 and BIU87 cells under radiation. Moreover, TUG1 depletion suppressed the HMGB1 mRNA and protein levels. Furthermore, overexpression of HMGB1 reversed TUG1 knockdown-induced effect in bladder cancer cells. Radiation treatment dramatically reduced the tumor volume and weight in xenograft model, and this effect was more obvious when combined with TUG1 silencing. CONCLUSION: LncRNA TUG1 knockdown enhances radiosensitivity of bladder cancer by suppressing HMGB1 expression. TUG1 acts as a potential regulator of radioresistance of bladder cancer, and it may represent a promising therapeutic target for bladder cancer patients.	bladder
Plasmacytoid Urothelial Carcinoma of the Urinary Bladder: A Clinicopathologic and Immunohistochemical Analysis of 49 Cases.	OBJECTIVES: Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare histologic variant. We retrospectively analyzed a large series of bladder PUC from a single institution. METHODS: The patients consisted of 44 men and five women with a mean age of 62 years (range, 45-86 years). RESULTS: PUC was pure in 23 cases and mixed with other histologic types in 26 cases. All PUCs diffusely invaded the bladder wall. Most PUCs lacked immunoreactivity for the retinoblastoma (RB) gene protein (12/32) and E-cadherin (8/30). Of the 44 patients with follow-up information, 25 died of PUC at a mean of 23 months, whereas 19 patients were alive at a mean of 22 months. CONCLUSIONS: Our findings support that bladder PUC is a highly aggressive disease. The lack of E-cadherin expression in PUCs may underlie the distinct discohesive histologic appearance, and abnormal function of the RB gene may be implicated in the development of PUC.	bladder
E3 Ligase cIAP2 Mediates Downregulation of MRE11 and Radiosensitization in Response to HDAC Inhibition in Bladder Cancer.	The MRE11/RAD50/NBS1 (MRN) complex mediates DNA repair pathways, including double-strand breaks induced by radiotherapy. Meiotic recombination 11 homolog (MRE11) is downregulated by histone deacetylase inhibition (HDACi), resulting in reduced levels of DNA repair in bladder cancer cells and radiosensitization. In this study, we show that the mechanism of this downregulation is posttranslational and identify a C-terminally truncated MRE11, which is formed after HDAC inhibition as full-length MRE11 is downregulated. Truncated MRE11 was stabilized by proteasome inhibition, exhibited a decreased half-life after treatment with panobinostat, and therefore represents a newly identified intermediate induced and degraded in response to HDAC inhibition. The E3 ligase cellular inhibitor of apoptosis protein 2 (cIAP2) was upregulated in response to HDAC inhibition and was validated as a new MRE11 binding partner whose upregulation had similar effects to HDAC inhibition. cIAP2 overexpression resulted in downregulation and altered ubiquitination patterns of MRE11 and mediated radiosensitization in response to HDAC inhibition. These results highlight cIAP2 as a player in the DNA damage response as a posttranscriptional regulator of MRE11 and identify cIAP2 as a potential target for biomarker discovery or chemoradiation strategies in bladder cancer. Cancer Res; 77(11); 3027-39. ©2017 AACR.	bladder
[Chemotherapy against bladder cancer in geriatric patients].	The number of geriatric bladder cancer patients is now increasing in spite of little is known regarding the safety and efficacy of standard treatment for the patients due to luck of data in geriatric patients. Although they should be treated by modified standard treatment adjusted for their deteriorated physical activity, such treatment regimens are not established. Bladder preservation therapy could be recommended for geriatric patients with invasive bladder can- cer, which shows comparable survival benefit with radical cystectomy. Although chemother- apy could be a treatment option for geriatric patients, geriatric assessment before treatment is recommended to choose appropriate candidates to modify therapeutic regimens. Standard treatment for geriatric patients with cancer would be established based on clinical trials in- volving geriatric assessment.	bladder
[Surgical treatment of bladder cancer in the geriatric patients].	As bladder cancer is an age-related disease and an increase in patients with MIBC seems inevitable because of the aging population in Japan, muscle-invasive bladder cancer (MIBC) care in the elderly is likely to become a very common problem in daily practice. The gold standard for patients with MIBC is radical cystectomy (RC). However, elderly patients present with several comorbidities, and the geriatric patients with MIBC were not given po- tentially curative treatments, including RC. The optimal therapy for elderly MIBC patients may become a crucial issue. To achieve a better oncologic outcome in the neoadjuvant set- ting, the chemotherapy regimen should be less toxic to prevent any treatment-related delay between chemotherapy and RC. In addition, minimally invasive surgical approaches for the elderly patients with MIBC have been rapidly adopted for the treatment of MIBC, improving perioperative morbidity and ease of recovery.	bladder